3gj9

From Proteopedia

(Difference between revisions)

Revision as of 07:25, 25 December 2014

crystal structure of TIP-1 in complex with c-terminal of Kir2.3

Structural highlights

3gj9 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	3diw, 3dj1, 3dj3
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[TX1B3_HUMAN] May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.^[1] ^[2] ^[3] [IRK4_HUMAN] Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity).

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Inwardly rectifying potassium channel 2.3 (Kir2.3) is specifically targeted on the basolateral membranes of epithelial and neuronal cells, and it thus plays an important role in maintaining potassium homeostasis. Tax-interacting protein-1 (TIP-1), an atypical PDZ-domain-containing protein, binds to Kir2.3 with a high affinity, causing the intracellular accumulation of Kir2.3 in cultured epithelial cells. However, the molecular basis of the TIP-1/Kir2.3 interaction is still poorly understood. Here, we present the crystal structure of TIP-1 in complex with the C-terminal Kir2.3-peptide (residues 436-445) to reveal the molecular details of the interaction between them. Moreover, isothermal titration calorimetry experiments show that the C-terminal Kir2.3-peptide binds much more strongly to TIP-1 than to mammalian Lin-7, indicating that TIP-1 can compete with mammalian Lin-7 to uncouple Kir2.3 from its basolateral membrane anchoring complex. We further show that the phosphorylation/dephosphorylation of Ser443 within the C-terminal Kir2.3 PDZ-binding motif RRESAI dynamically regulates the Kir2.3/TIP-1 association in heterologous HEK293T cells. These data suggest that TIP-1 may act as an important regulator for the endocytic pathway of Kir2.3.

Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1.,Yan X, Zhou H, Zhang J, Shi C, Xie X, Wu Y, Tian C, Shen Y, Long J J Mol Biol. 2009 Oct 2;392(4):967-76. Epub 2009 Jul 25. PMID:19635485^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Reynaud C, Fabre S, Jalinot P. The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in Rho signaling to the serum response element. J Biol Chem. 2000 Oct 27;275(43):33962-8. PMID:10940294 doi:10.1074/jbc.M000465200
↑ Alewine C, Olsen O, Wade JB, Welling PA. TIP-1 has PDZ scaffold antagonist activity. Mol Biol Cell. 2006 Oct;17(10):4200-11. Epub 2006 Jul 19. PMID:16855024 doi:10.1091/mbc.E06-02-0129
↑ Oliver AW, He X, Borthwick K, Donne AJ, Hampson L, Hampson IN. The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, which activates Cdc42. Br J Cancer. 2011 Jan 18;104(2):324-31. doi: 10.1038/sj.bjc.6606026. Epub 2010, Dec 7. PMID:21139582 doi:10.1038/sj.bjc.6606026
↑ Yan X, Zhou H, Zhang J, Shi C, Xie X, Wu Y, Tian C, Shen Y, Long J. Molecular mechanism of inward rectifier potassium channel 2.3 regulation by tax-interacting protein-1. J Mol Biol. 2009 Oct 2;392(4):967-76. Epub 2009 Jul 25. PMID:19635485 doi:10.1016/j.jmb.2009.07.060

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3gj9"

@@ Line 7: / Line 7: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gj9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gj9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gj9 RCSB], [http://www.ebi.ac.uk/pdbsum/3gj9 PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/TX1B3_HUMAN TX1B3_HUMAN]] May regulate a number of protein-protein interactions by competing for PDZ domain binding sites. Binds CTNNB1 and may thereby act as an inhibitor of the Wnt signaling pathway. Competes with LIN7A for KCNJ4 binding, and thereby promotes KCNJ4 internalization. May play a role in the Rho signaling pathway. May play a role in activation of CDC42 by the viral protein HPV16 E6.<ref>PMID:10940294</ref> <ref>PMID:16855024</ref> <ref>PMID:21139582</ref>  [[http://www.uniprot.org/uniprot/IRK4_HUMAN IRK4_HUMAN]] Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

3gj9

From Proteopedia

Revision as of 07:25, 25 December 2014

crystal structure of TIP-1 in complex with c-terminal of Kir2.3

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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